Marek's disease is a malignant lymphoproliferative disease of chickens, caused by an infection with Marek's disease virus, belonging to Avian Herpesvirus serotype-1 (Avian Pathology 4: 133-146, 1975). First recognized in 1907, it is still the most destructive of the poultry viruses.
The invention relates to a highly immunogenic and non-pathogenic virus preparation derived from Marek's disease virus (MDV) strain CVI-988, belonging to Avian Herpesvirus serotype-1, by serial passage in avian cell cultures and plaque purification. The original virus isolate, the parent strain MDV CVI-988, was recovered from a healthy laboratory chicken as an isolate of low virulence which could be attenuated by serial passages in cell cultures (Rispens et al. in Avian Diseases 16, pages 108-125 and 126-138 (1972)). Since then, the virus preparation obtained after about 35 passages in avian cell cultures has been used succesfully for vaccination of chickens against Marek's disease (MD). Initially, the virus attenuation had been carried out in duck embryo fibroblasts (DEF). However, ducks are difficult to maintain under specific pathogen free (SPF) conditions. This necessitates extensive testing of every production batch in order to guarantee the absence of micro-organisms pathogenic to birds. Maintenance of chickens under SPF conditions creates less problems. Moreover, chicken cells are preferred because they will not introduce, into the MD vaccines, cells foreign to the animal species. Consequently, in the period of 1967-1978 the MDV CVI-988 strain was adapted to chick embryo fibroblast cell cultures (CEF) and the MDV CVI-988 vaccine producers switched to vaccine production in CEF.
Although, in practice, vaccines based on the parent strain MDV CVI-988 provide highly satisfactory results via intramuscular administration (Maas et al., World Poultry Sci. 38, 163-176 (1982)), subcutaneous application is less effective, it may provoke MD lesions in chickens of the strain of highly MD susceptible SPF Rhode Island Red (RIR) chickens, when these chickens are inoculated with ten times the normal field dose (Avian Pathology, 6, 395-403 (1977)).
In JAVMA vol. 183, page 355, K. A. Schat, et al. reported that a new clone of the JM strain of Marek's disease (JM-16) and certain of its subclones did not induce tumors, but immunogenicity was not discussed.
On the same page G. F. De Boer et al. discussed an MDV CVI-988 clone obtained by passage in cell cultures and plaque purification of MDV CVI-988. Passages no. 51 and no. 97 were safe in RIR chickens, and effective protection was obtained in a small number of vaccination trials with passage no. 51, but not with passage no. 97. Passage no. 51 gave about the same degree of protection as the commercial parent vaccine (passage no. 35). The abstract did not disclose any deposit numbers under which cultures of these new clones might be requested. Moreover, the clones discussed have been found to be inferior to CVI-988 CEF.sub.65 clone C in immunogenicity.
Other vaccines against Marek's disease in use are:
A. A vaccine based on a Turkey Herpesvirus (HVT FC126), ((Avian Diseases 14, pages 413-429 (1970)) and U.S. Pat. No. 3,642,574)) belonging to Avian Herpesvirus serotype-3. Application in cell-free form of this vaccine is described in U.S. Pat. No. 3,783,098.
B. A vaccine obtained by attenuation of a virulent MDV strain (HPRS-16), ((Journal of General Virology 4, 557-564 (1969) and U.S. Pat. No. 3,674,861)) belonging to Avian Herpesvirus serotype-1.
C. A vaccine based on a non-oncogenic virus strain of Marek's disease virus of serotype-2 (SB-1), ((Journal National Cancer Institute 60, 1075-1082 (1978), and U.S. Pat. No. 4,160,024)). This vaccine to be effective is generally applied as a mixture with HVT vaccine.